Time of neuron origin in the hippocampal region: An autoradiographic study in the mouse

Abstract

Time of origin (final cell division) of neurons in the hippocampal region of the mouse cerebral hemisphere was determined by autoradiography. Forty-two animals were injected with thymidine-H 3 at various developmental stages and killed, in most instances, at maturity. Neuron formation for the entire region begins on the tenth embryonic day; thereafter the neurons in all components but one arise in a general, but not rigid, “inside-out” sequence. These observations demonstrate active displacement and migration of neuroblasts; in late developmental stages long migrations occur. The area entorhinalis, parasubiculum, area retrosplenialis e, subiculum, hippocampal sector CA2, and molecular and hilar layers of area dentata complete their periods of neuron formation by embryonic day 15, the presubiculum by day 16. In sharp contrast, the pyramidal cells of hippocampal sectors CA1 and CA3 continue to arise until birth (embryonic day 19) and the granule cells of area dentate until postnatal day 20. Sequence of neuron formation in stratum granulosum, unlike all other cortical areas or layers studied, is “outside-in”. Granule cells originating prenatally or perinatally migrate to stratum granulosum from the primitive ependyma or a proliferative region in the hippocampal stratum oriens, respectively. Postnatally, granule cells arise by proliferation of deeply situated neuroblasts in stratum granulosum itself. The highly individual calendars of neuronal birthdays for the various component areas accord with the rigorous timing of neuroblast migrations stressed by Levi-Montalcini and also coincide with accepted areal boundaries. The possibility that connections might be established between migrating neuroblasts is considered, but no evidence is presented. Persistence of neuron formation in stratum granulosum of area dentate supports Elliot Smith's interpretation that the fascia dentata represents a localized hypertrophy of the superficial cortical layers. The early completion of neuron formation for the hilus fasciae dentatae when compared with CA3 strengthens Blackstad's concept of an area dentata. The granule cells of area dentata and the pyramidal cells of CA3 and CA1 are the last neurons of the hippocampal region to arise. This common feature is of interest because these neurons form a functional system, by means of the mossy fiber and Schaffer axon collaterals, which phylogenetically shows striking elaboration in the placental mammals.